Ion channels are transmembrane multi-subunit proteins embedded in the cellular plasma membranes of living cells which permit the passage of specific ions from the extracellular side of the plasma membrane to the intracellular region of the cell. Specific ion transport is facilitated by a central aqueous pore which is capable of opening and closing due to changes in pore conformation. When the ion gate is open, ions flow freely through the channel. When the ion gate is closed, ions are prevented from permeating the channel. Ion channels are found in a multitude of multicellular eukaryotic species and in a myriad of different cell types. Ion channels may be either voltage-gated or ligand-gated. Channel gating is the process by which a particular channel is either open or closed. An ion channel may be capable of occupying a range of different “open” or “closed” states. The gating process may therefore require a particular sequence of transition states or inclusion of alternative transition states before a channel attains a particular level of gating. The gating process is modulated by a substance or agent, which in some way alters or affects the manner in which the channel opens or closes. A channel may be gated by a ligand such as a neurotransmitter, an internal primary or secondary messenger, or other bioactive agent. The ligand either attaches to one or more binding sites on the channel protein or attaches to a receptor that is associated with the channel. If the channel is voltage-gated, changes in the membrane potential trigger channel gating by conformational changes of charged elements within the channel protein. Whether a channel is ligand-gated or voltage-gated, a change in one part of the channel produces an effect in a different part of the channel which results in the opening or closing of a permeant pathway.
The non-selective transmembrane channel polypeptides form a family of cation channels comprised of seven members TRPC1-TRPC7. The channel proteins are further divided into three main subfamilies: S for Short nonselective transmembrane channels, L for long non-selective transmembrane channels, and O for Osm-9-like non-selective transmembrane channels. Although the non-selective ion channel proteins are widely distributed in mammalian tissues, the specific physiological properties of the channels remain largely unknown. The protein subunits of the non-selective transmembrane channels have six transmembrane domains predicted to assemble into tetramers for forming ionic channels. The slightly hydrophobic amino acids which link the fifth and sixth transmembrane domain are purported to line the pores of the channels. Amino terminal and carboxyl terminal domains of the non-selective protein comprise the intracytoplasmic region of the channel. In spite of similarities in structure, the functions of the non-selective channel proteins differ between members of the same polypeptide family. Studies demonstrate that each channel has a unique ion selectivity and a particular mechanism for activation.